Phenoxybenzamine is used as an anti-hypertensive due to its efficacy in reducing the vasoconstriction caused by adrenaline and noradrenaline. Phenoxybenzamine forms a permanent covalent bond with adrenergic receptors. Based on what we know about the structures of these receptors, it likely involves attack by the cysteine at position 3.36 in transmembrane helix 3 to form a stable linkage.[3] Thus, it remains permanently bound to the receptor, preventing adrenaline and noradrenaline from binding. This causes vasodilatation in blood vessels, due to its antagonistic effect at the alpha-1 adrenoceptor found in the walls of blood vessels, resulting in a drop in blood pressure.

It will also affect the postsynaptic alpha 1 and 2 receptors in the nervous system, and so reduce sympathetic activity. This results in further vasodilation, pupil constriction, an increase in GI tract motility and secretions, and glycogen synthesis.